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Oxidative stress occurs in diabetic patients and experimental models of diabetes. The ability of l-arginine to ameliorate the oxidative stress and metabolic changes after treatment with alloxan was investigated in rats. Adult male rats were injected intraperitoneally with 100 mg kg(-1) of alloxan to produce experimental oxidative stress characteristic of diabetes mellitus. Hyperglycaemia and hypercholesterolaemia were observed in serum after 7 days of alloxan treatment. This was associated with a depression of glutathione (GSH) concentration as well as superoxide dismutase (SOD) and catalase (CAT) activities in the liver and brain. In addition, the thiobarbituric acid-reactive substances (TBARS) were significantly elevated, indicating increased lipid peroxidation and oxidative stress in the same tissues. Administration of 100 mg kg(-1) l-arginine for 7 days either before or after alloxan injection significantly ameliorated the oxidative stress evidenced by a lower TBARS and a higher level of the endogenous GSH concentration and SOD and CAT activities than alloxan-treated rats. These effects were paralleled by marked protection and partial prophylaxis against alloxan-induced hyperglycaemia and cholesterolaemia. Thus, these results showed that exogenously administered l-arginine might improve the clinical manifestation of diabetes mellitus and decrease the oxidative stress in the liver and brain. In addition, the study supports the beneficial effect of l-arginine, which might be attributed to its direct, NO-dependent antioxidant capacity and/or NO-independent pathways.

Cardiomyopathy and pancreatic injury are health issues associated with type 2 diabetes mellitus (T2DM) and are characterized by elevated oxidative stress, inflammation and apoptosis. Melatonin (MLT) is a hormone with multifunctional antioxidant activity. The protective effects of MLT on the heart and pancreas during the early development of diabetic cardiomyopathy and pancreatic injury were investigated in male Wistar rats with T2DM. MLT (10 mg/kg) was administered daily by gavage for 15 days after diabetic induction. Treatment of diabetic rats with MLT significantly normalized the levels of serum glucose, HbA1-c, and the lipid profile and improved the insulin levels and insulin resistance compared with diabetic rats, affirming its antidiabetic effect. MLT significantly prevented the development of oxidative stress and sustained the levels of glutathione and glutathione peroxidase activity in the heart and pancreas of diabetic animals, indicating its antioxidant capacity. Additionally, MLT prevented the increase in proinflammatory cytokines and expression of Bax, caspase-3 and P53. Furthermore, MLT enhanced the anti-inflammatory cytokine IL-10 and antiapoptotic protein Bcl-2. MLT controlled the levels of troponin T and creatine kinase-MB and lactate dehydrogenase activity, indicating its anti-inflammatory and antiapoptotic effects. Histological examinations confirmed the protective effects of MLT on T2DM-induced injury in the myocardium, pancreas and islets of Langerhans. In conclusion, the protective effects of melatonin on the heart and pancreas during the early development of T2DM are attributed to its antihyperglycemic, antilipidemic and antioxidant influences as well as its remarkable anti-inflammatory and antiapoptotic properties.

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2015) Cardioameliorative effect of punicalagin against streptozotocin-induced apoptosis, redox imbalance, metabolic changes and inflammation, A B S T R A C TThe effect of punicalagin on metabolic risks, oxidative stress, inflammation, cardiac apoptosis and histopathological alterations in experimentally induced diabetes was addressed. Diabetes was induced in male rats by a single injection of streptozotocin (STZ; 40 mg/kg, i.p.), and then punicalagin (1 mg/kg) was i.p. administered every other day for 15 days. The diabetic rats treated with punicalagin exhibited ameliorated hyperglycemia and HbA1c; improved insulin levels, HOMA-IR levels and lipid profiles; and normalized levels of IL-1b, IL-6 and TNF-α. Punicalagin also reduced the increase in the MDA and H2O2 levels; normalized the levels of GSH, SOD and CAT in the heart; and improved serum markers of heart function including the levels of troponin T level and CK-MB and LDH activities. Histopathological examinations of heart sections match these results, confirming the beneficial effect of punicalagin. It also modulated cardiomyocyte apoptosis via enhanced Bcl-2 expression; blocked the increases in P53, Bax and caspases-3, 8 and 9; and ameliorated DNA damage in the heart. The current results suggest that punicalagin protected the heart against apoptosis, necrosis, inflammation and DNA damage by improving the redox state, suppressing caspases and P53 and increasing Bcl-2. In conclusion, punicalagin possesses strong therapeutic potential in treating and regulating diabetes and attenuating its associated complications in the heart.